Dengue virus (DENV) infection remains an international public health problem affecting urban populations in tropical and sub-tropical regions, where it is currently estimated that about 2.5 billion people are at risk. Dengue virus is a single positive-stranded RNA virus of the family Flaviviridae, genus Flavivirus, which is transmitted among humans primarily by Aedes aegypti mosquitoes. In humans, dengue infection can produce diseases of a wide spectrum of severity, ranging from asymptomatic to flu-like dengue fever (DF), and life-threatening dengue hemorrhagic fever (DHF) (Martina et al. Clin. Microbiol. Rev. 22:564-81, 2009) or dengue shock syndrome (DSS). DHF is particularly associated with capillary leakage, hemorrhage, circulatory shock, and consequently increased mortality.
Due to a number of factors, including increasing urbanization and globalization of travel, dengue disease is re-emerging in the Americas (Pinheiro and Corber, World Health Stat. Q. 50:161-69, 1997). The mortality of DHF is age-dependent, primarily affecting both children and the elderly (Guzman et al., Int. J Infect. Dis 6:118-24, 2002). In Southeast Asia, a disproportionate amount of DHF hospitalizations are of children whereas in the Americas, there is a more even distribution across ages.
While DHF fatality rates can exceed 20%, early and intensive supportive therapy has reduced it to less than 1% (Ranjit et al., Aggressive management of dengue shock syndrome may decrease mortality rate: A suggested protocol. Pediatric Critical Care Medicine 6:6, 2005). Therefore, early detection and differentiations of dengue disease types can be used for the prognosis and treatment of patients presenting with dengue-like symptoms. Additional methods and combinations of biomarkers to identify DHF are needed.